Amyloidosis as a cause of death in patients with rheumatoid arthritis

OBJECTIVE: To study amyloidosis as a cause of death along with associated factors and frequency of pre-mortem diagnosis in patients with rheumatoid arthritis (RA) autopsied between 1952 and 1991. METHODS: We studied causes of death in 369 consecutively autopsied RA and 370 autopsied non-RA patients of the same sex, age at death, and year of autopsy. In those RA patients who died from 1973 onwards, we were also able to analyse clinical data: pre-mortem diagnosis of amyloidosis, clinical features of RA, and treatment. RESULTS: Based on autopsy, amyloidosis was determined as a cause of death in 9.5% of RA and in none of the non-RA patients (p<0.001). In our RA patients, we detected no trend in deaths from amyloidosis between 1952 and 1991. The RA patients dying of amyloidosis died younger than those dying of other causes (p=0.001). During the course of the disease, the RA patients with amyloidosis had: higher erythrocyte sedimentation rate (p=0.002), lower haemoglobin (p<0.001), more frequently proteinuria (p<0.001) and renal failure (p<0.001) than did the rest of the RA patients. Pre-mortem, amyloidosis was diagnosed by biopsy in 65% of the RA patients with amyloidosis as their cause of death. CONCLUSION: Amyloidosis may be undetected during the course of RA. Thus, it should be actively searched for in the patients with long-lasting and active disease, especially, if they have proteinuria or renal failure.     

Causes of death in patients with rheumatoid arthritis autopsied during a 40-year period

We studied causes of death (CoDs) between 1952 and 1991 assessed by a clinician before autopsy and then determined at autopsy by a pathologist in 369 subjects with rheumatoid arthritis (RA) and 370 subjects without RA (non-RA). We analysed clinical data for RA subjects between 1973 and 1991. In RA subjects, leading autopsy-based CoDs were RA, cardiovascular diseases and infections. Between diagnoses of CoDs by the clinician and those determined by the pathologist, RA subjects had lower agreement than did the non-RA regarding coronary deaths (Kappa reliability measure: 0.33 vs. 0.46). In non-RA subjects, autopsy-based coronary deaths showed a decline since the 1970s with no such decline in RA. Between subjects treated at any time during RA with disease-modifying anti-rheumatic drugs and those without, autopsy-based CoDs were similar. Coronary death being less accurately diagnosed in RA subjects may indicate that coronary heart disease in RA patients often remains unrecognized.     

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Prevalence of AA amyloid in rheumatoid arthritis (RA) is still unclear. The objective of this retrospective study was whether dedicated re-examination of autopsy tissues from RA patients increases the detection rate of amyloid compared to routine examination. Amyloid was re-examined in tissue samples and detection rate compared with original reports of 369 consecutively autopsied RA patients and 370 non-RA patients matched for sex, age, and year of autopsy between 1952 and 1991. Re-examination of 90% of the 739 cases showed doubling of the prevalence of amyloid compared with the original reports: from 18 to 30% in RA and from 2 to 4% in non-RA patients. In RA patients, cardiac amyloid was as frequent as renal amyloid. In RA patients with amyloid at re-examination, amyloidosis had been diagnosed before autopsy in 37%, and these patients had more inflammation and longer disease duration than RA patients without amyloid. Only 56% of RA patients with renal amyloid were known to have proteinuria. In conclusion, this autopsy study shows that amyloid in RA is a common finding which remains frequently undetected. In patients with active and long-lasting RA, a systematic search for amyloid may enable early diagnosis of amyloidosis, which will require effective suppression of inflammation.     

Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study

OBJECTIVE: A high frequency of infections complicating rheumatoid arthritis (RA) has been described in reports of case series. This retrospective longitudinal cohort study was undertaken to compare the frequency of infections in a population-based incidence cohort of RA patients with that in a group of individuals without RA from the same population. METHODS: RA patients included all members of an incidence cohort of Rochester, Minnesota residents ages >or=18 years who were first diagnosed as having RA between 1955 and 1994. One age- and sex-matched subject without RA was selected for each patient with RA. Study subjects were followed up by review of their entire medical record until death, migration from the area, or study end (January 1, 2000), and details of all documented infections, along with information on potential risk factors for infection, were recorded. Hazard ratios for infections were estimated using stratified Andersen-Gill proportional hazards models, with adjustment for potential confounders. RESULTS: The 609 RA patients and 609 non-RA study subjects (mean age 58.0 years; 73.1% female) were followed up for a mean of 12.7 years and 15.0 years, respectively, reflecting higher mortality among the group with RA. Hazards ratios for objectively confirmed infections, infections requiring hospitalization, and any documented infection in patients with RA were 1.70 (95% confidence interval [95% CI] 1.42-2.03), 1.83 (95% CI 1.52-2.21), and 1.45 (95% CI 1.29-1.64), respectively, after adjustment for age, sex, smoking status, leukopenia, corticosteroid use, and diabetes mellitus. Sites of infection with the highest risk ratios were bone, joints, skin, soft tissues, and the respiratory tract. CONCLUSION: In this study, patients with RA were at increased risk of developing infections compared with non-RA subjects. This may be due to immunomodulatory effects of RA, or to agents with immunosuppressive effects used in its treatment.     

A single center 14 years study of infectious complications leading to hospitalization of patients with primary antibody deficiencies

Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterized by hypogammaglobulinemia and increased susceptibility to bacterial infections, leading to hospitalizations. This study was performed to determine the main infectious causes of hospital admissions in selective Iranian patients with PADs. Forty patients with PADs, who were admitted to the Infectious Ward of Children's Medical Center Hospital during a 14-year period, were reviewed in this study. There were 115 documented episodes of hospital admission during a 14-year period. The average length of hospital stay was 33.30 ± 25.72 days. Pneumonia was the most prominent infection leading to hospitalization among these patients (n = 48), followed by gastroenteritis (n = 23). Other less frequent causes of hospitalization were fever and neutropenia, septic arthritis, encephalitis, orbital cellulitis, sepsis, urinary tract infection, meningitis, oral ulcer, and lung abscess. The most common causative organisms of diarrhea were: Giardia lamblia, followed by Candida albicans, and Salmonella sp. Many patients with PADs suffer from repeated infections leading to hospitalization, in spite of immunoglobulin replacement therapy. Respiratory tract infections were the prominent cause of hospitalization among studied patients, followed by gastrointestinal infections.     

Pneumocystis jirovecii pneumonia in African miners at autopsy.

SETTING: Deceased miners from South Africa whose cardio-respiratory organs were submitted for autopsy for compensation for occupational lung diseases from 1996 to 2000. OBJECTIVES: 1) To document the incidence of Pneumocystis jirovecii pneumonia (PJP) in autopsied miners; 2) to compare the incidence of PJP over a 5-year period; 3) to record the incidence of concomitant lower respiratory tract infection in a group of PJP-infected deceased miners coming to autopsy from 1996 to 2000; and 4) to describe the accuracy of the in-life diagnosis of PJP in this group. DESIGN: Case series of 328 deceased Black miners with histological evidence of PJP at autopsy. RESULTS: Of the 328 miners with PJP at autopsy, 107 (32.6%) had a concomitant respiratory infection, the most common being cryptococcal pneumonia (46.7%), followed by bacterial pneumonia (34.6%) and pulmonary tuberculosis (13.1%). Overall, Pneumocystis pneumonia was unsuspected prior to death in 89% of cases; however, diagnostic accuracy in life improved from 7% in 1996 to 21% in 2000. CONCLUSION: The high rate of undiagnosed PJP is cause for concern. Clinicians should have a heightened awareness for PJP in Africa, particularly as the disease is treatable at low cost and effective prophylaxis is available.     

Infectious complications of cirrhosis

Infectious complications in cirrhotic patients can cause severe morbidity and mortality. Bacterial infections are estimated to cause up to 25% of deaths in cirrhotic patients. The most frequent are urinary tract infection, spontaneous bacterial peritonitis, respiratory tract infection, and bacteremia. It has been said that cirrhosis is the most common form of acquired immunodeficiency, exceeding even AIDS. The specific risk factors for infection in cirrhotic patients are low serum albumin, gastrointestinal bleeding, intensive care unit admission for any cause, and therapeutic endoscopy. Certain infectious agents are more virulent and more common in patients with liver disease. These include Vibrio, Campylobacter, Yersinia, Plesiomonas, Enterococcus, Aeromonas, Capnocytophaga, and Listeria species, as well as organisms from other species. Spontaneous bacterial peritonitis is a frequent, severe, life-threatening complication of patients with ascites. Current observations and recommendations regarding treatment and prophylaxis are reviewed. A brief synopsis of miscellaneous infections encountered in cirrhotic patients is also included.     

Causes of death in patients with rheumatoid arthritis--analysis of 117 cases for 13 years

One hundred seventeen deaths of RA patients (30 males and 87 females) at National Sagamihara Hospital for 13 years (1975-1988) were analysed. The average duration of disease were 10.5 years in male patients and 17.7 years in female. The average life span of the patients with RA, revealing 65.8 years in male and 63.7 years in female, were much shorter than of general population. The causes of all deaths were investigated by ourselves and/or autopsy. The autopsy was performed in 56.6%. The most common causes of death in RA patients were infectious diseases (20.5%), respiratory diseases (16%, mainly interstitial pneumonia and chronic obstructive lung diseases), and gastrointestinal diseases (14.7% chiefly perforation or bleeding of peptic ulcer). The distribution of causes of death in RA patients was quite different from in general population. The gastrointestinal disease decreased from 20% in the early half (1975-1981) to 12.6% in the latter half (1982-1987). It seems likely that H2-receptor antagonist played a major role for preventing the death by perforation or bleeding of ulcer, because the drug has been used since 1982 in Japan. Renal insufficiency including amyloidosis increased markedly in the latter half (14.9%) compared with in the early half (6.7%). Frequency of infectious diseases, respiratory diseases, and basilar impression remain unchanged in all course. Although our study are case-analysis in only one institute and further study will be necessary, the accumulation of the data investigated by rheumatologist will be helpful to grasp correct cause of death in patients with RA.     

Infectious complications after kidney transplantation: a single-center experience

Infectious complications after renal transplantation are associated with significant morbidity and mortality. The prevalence of infections in transplant recipients varies from country to country. This study sought to assess the overall incidence of post-transplant infectious complications at our research center in Iran, compared with other centers in the world. Between 2002 and 2004, 179 renal transplantations were performed in our center. Of these, 142 were studied and followed for 1 year. Immunosuppressive regimens were cyclosporine, mycophenolate mofetil, and prednisolone. The overall incidence of infections was 54.2%. The most common sites of infections were the urinary tract (41.5%) and the respiratory tract (6.3%). The most frequent causes of infections were Klebsiella (24%) and cytomegalovirus (CMV) (17.6%). Wound infection occurred in 4.9% of the patients. Three (2.1%) patients developed hepatitis C and 2 (1.4%) had mycobacterial infections. There was no case of Pneumocystis pneumonia. Overall mortality was 7.7%. Infection-related mortality was 3.5%. In conclusion, this study identifies infections as the cause of morbidity and mortality in the post-transplant period. There was a low incidence of tuberculosis (<2% yearly) and a high incidence of CMV disease in our recipients.     

Urinary tract infections and chronic renal failure

The paper briefly summarizes issues related to urinary tract infections in adults: predispositions and risk factors, classification, assessment of pathogenicity of bacterial agents, the role of bacteriuria and leucocyturia, interpretation of findings, treatment principles and an association with chronic renal failure. Urinary tract infections are the second most frequent infectious disease in the population. They most often affect women of childbearing potential and then seniors of both sexes who have multiple risk factors. Escherichia coli and Staphylococcus saprophyticus are the most pathogenic towards urinary tract; they are responsible for 85% and 10-15% of cases of acute uncomplicated urinary infections, respectively. Chronic pyelonephritis, a chronic interstitial nephritis, is the fourth most frequent cause of chronic renal failure. Chronic renal failure is a risk factor for the development of urinary infections due to metabolic disorders resulting in secondary immunodeficiencywith a disorder of all components of immunity. In patients with chronic renal failure, urinary tract infections occur most frequently after kidney transplantation when graft pyelonephritis is a life-threatening complication. Therefore, urinary tract infection prevention with co-trimoxazole once daily over at least 6 months is recommended in renal allograft recipients.     

Antimicrobial Resistance and Aging: Beginning of the End of the Antibiotic Era?

Throughout the history of mankind, infectious diseases have remained a major cause of death and disability. Although industrialized nations, such as the United States, have experienced significant reductions in infection-related mortality and morbidity since the beginning of the "antibiotic era," death and complications from infectious diseases remain a serious problem for older persons. Pneumonia is the major infection-related cause of death in older persons, and urinary tract infection is the most common bacterial infection seen in geriatric patients. Other serious and common infections in older people include intra-abdominal sepsis, bacterial meningitis, infective endocarditis, infected pressure ulcers, septic arthritis, tuberculosis, and herpes zoster. As a consequence, frequent prescribing of antibiotics for older patients is common practice. The large volume of antibiotics prescribed has contributed to the emergence of highly resistant pathogens among geriatric patients, including methicillin-resistant Staphylococcus aureus , penicillin-resistant Streptococcus pneumoniae , vancomycin-resistant enterococci, and multiple-drug-resistant gram-negative bacilli. Unless preventive strategies coupled with newer drug development are established soon, eventually clinicians will be encountering infections caused by highly resistant pathogens for which no effective antibiotics will be available. Clinicians could then be experiencing the same frustrations of not being able to treat infections effectively as were seen in the "pre-antibiotic era."     

Deaths from nosocomial infections: Experience in a university hospital and a community hospital

To assess the importance of nosocomial infections as a contributory cause of death in patients who die in the hospital, we studied the hospital course of 100 consecutive patients who died at Columbia-Presbyterian Medical Center and 100 consecutive patients who died at Hackensack Hospital. The epidemiologic patterns of infection were similar although the institutions provide care for different types of patients. There were 88 nosocomial infections in 63 patients. When the nosocomial infection was causally related or contributed to death, infection of the lower respiratory tract was predominant in 31 of 52 (60 per cent) instances. When the nosocomial infection was unrelated to death, urinary tract infection was predominant in 13 of 36 (36 per cent) infections. Among those who died with nosocomial infection, 42 of 63 (67 per cent) patients were terminal on admission and were typically in their 60's with metastatic carcinoma. The 21 patients who were not terminal on admission were typically in their late 70's and had complications of arteriosclerotic cardiovascular disease. Pneumonia was the most frequent nosocomial infection related to death. There is need to devise a pneumonia prevention program that identifies those at high risk and reduces the chance of aspiration of pharyngeal secretions and spread of virulent bacteria from person to person.     

A comparison of community-acquired lung infection and nosocomial infection--review of autopsy cases in Hisayama town]

All people in Hisayama town who died either at home or in hospital are autopsied in Kyushu University Hospital. We examined the incidence and the pathogen of community-acquired lung infection and nosocomial infection from the records of 463 autopsy cases from 1977 to 1988. Of these cases, 243 died at home. Among them, pulmonary infections were present in 122 cases (50.2%), and pulmonary infection was the cause of death in 87 cases (35.8%). Of 220 cases that died in hospital, pulmonary infections were present in 133 cases (60.5%) and were the cause of death in 83 cases (37.7%). In the cases that died at home, the incidence of pulmonary infections during the first 6-year period of the study was almost the same as that during the last 6 years. In the case that died in hospital, the incidence of pulmonary infections during the last 6-year period was higher than that during the first 6-year period. Regarding the pathogenic organisms of the fungal infections, only Candida was detected in case that died at home, while Candida, Aspergillus and Cryptococcus were detected in the case that died in hospital.     

Cause of death in older patients with anatomo-pathological evidence of chronic bronchitis or emphysema: a case-control study based on autopsy findings

OBJECTIVES: To determine the most frequent causes of death of hospitalized older patients based on anatomo-pathological evidence and to compare the relative frequency of fatal events between patients with and without evidence of either chronic bronchitis (CB) or emphysema (E). DESIGN: Retrospective, case-control study based on a computerized database including anatomo-pathological data of patients deceased and autopsied over a 25-year period. SETTING: Two geriatric hospitals in Geneva. PARTICIPANTS: Not applicable. MEASUREMENTS: Autopsy records for cause(s) of death in patients with CB or E. RESULTS: 3,685 patients deceased in our institution (1,540 men; 2,145 women) were autopsied between 1972 and 1996; mean age at death was 81.5 +/- 8.0 years. Anatomo-pathological evidence of CB or E was found in 983 patients (26.6% of total); 262 (7.2%) had predominantly CB, and 456 (12.3%) predominantly E. Pneumonia was the most frequent cause of death in all patients (21.8%). Myocardial infarction (MI) (17.6% vs 14%), and respiratory failure (5.1% vs 1.5%) occurred more frequently in subjects with CB and/or E than in controls. Fatal pulmonary embolism (PE) was more frequent in patients with E (18.4%) than in patients with CB (10.7%; odds ratio ( OR) = 1.89, P =.008), or in controls (12.7%; OR = 1.56, P =.0008). CONCLUSION: Anatomo-pathological evidence of CB or E is highly prevalent in older patients, suggesting that CB and E are clinically underdiagnosed in this age group. Fatal MI occurred significantly more frequently in older patients with E or CB than in controls. Furthermore, patients with E were at significantly higher risk of fatal PE than patients with CB or controls.     

Causes of death in patients with rheumatoid arthritis from 1971 to 1991 with special reference to autopsy

Rheumatoid arthritis (RA) patients have premature mortality, mostly attributed to cardiovascular diseases (CVDs). We studied causes of death (CoDs) and contribution of autopsy to them in RA patients treated at a single hospital responsible for primary to tertiary RA treatment in Helsinki. In 1971–1991, 960 RA patients died. The leading CoDs were CVDs, RA, and infections. Over 1971–1991, RA and renal deaths declined, but other CoDs showed no change. Autopsied patients died more frequently than nonautopsied of coronary heart disease (CHD) and gastrointestinal disorders, but less frequently of RA, renal, and endocrinologic diseases. Our finding of autopsied patients having CHD more frequently as a CoD may indicate that CHD, which may be asymptomatic in RA, may be overlooked during lifetime.     

A 12-month fever surveillance study in a veterans' long-stay institution

This report describes a 12-month fever surveillance survey in a 258-bed veterans long-term care institution. There were 128 episodes of fever (one episode per 24 patient-months); 114 were studied. Lower respiratory tract infections were most frequent, 36 (32%), with 26 (23%) urinary tract infections. Streptococcus pneumoniae was the most common pathogen in the chest infections and Proteus mirabilis the most common of the urinary tract infections. In 40 (35%) there was no evidence of a lower respiratory tract, urinary tract, or other bacterial infection. Most recovered rapidly, many with no specific treatment. There was a 16% mortality associated with the febrile episodes.     

Death rate and causes of death in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis, 500 males and 500 females, aged 40 years or over, and an age- and sex-matched control population were observed over a 3-year period. During the follow-up, 122 RA patients and 69 controls had died. The most common causes of death in RA patients were cardiovascular diseases (57 patients), renal failure (27 patients), infections (19 patients), and malignant neoplasms (11 patients); in the controls, the respective data are: cardiovascular diseases (35 people), malignant neoplasms (21 people), accidents (7 people), and infections (5 people).     

A study of consecutive autopsies in a medical ICU : a comparison of clinical cause of death and autopsy diagnosis

OBJECTIVE: To determine the degree of concordance between clinical cause of death and autopsy diagnosis in a medical ICU (MICU) setting. DESIGN: Retrospective medical chart and autopsy report review. SETTING: MICU in a tertiary referral hospital. PATIENTS: Consecutive admissions to an MICU over a 2-year period from January 1, 1994, to December 31, 1995. INTERVENTIONS: None. Measurements and main results: One thousand eight hundred patients were admitted to the MICU during the study period. There were 401 in-ICU deaths (22.3%). The autopsy rate was 22.7% (91 of 401). The mean +/- SD age of the autopsied patients (55.1 +/- 13.5 years) was lower than those without autopsy (62.4 +/- 15.2 years; p < 0.001). The two groups were otherwise similar with regard to sex, race, APACHE (acute physiology and chronic health evaluation) III scores, and lengths of stay in the MICU and hospital. The discordance between clinical and postmortem diagnoses was 19.8% (95% confidence interval, 12 to 29%). There were no differences in age, sex, APACHE III scores, predicted mortality, and lengths of stay in MICU hospital between patients with concordant and discordant diagnoses. In 44.4% (8 of 18) of the discordant cases, management would have been modified had the autopsied diagnosis been made premortem. Seven of the autopsied patients had organ transplantation. Three of the patients who had organ transplantation had discordant diagnoses, including two patients with disseminated fungal infection that was not diagnosed clinically. Although the observed discordance in transplant patients (43%) was higher than in those without transplant (19%), the difference was not statistically significant (p = 0.15). CONCLUSION: Younger patients tended to have a higher autopsy rate than older patients. The discordance between the clinical cause of death and postmortem diagnosis was 19.8%. In 44.4% of the discordant cases, knowledge of the correct diagnosis would have altered therapy.     

Epidemiology of intensive care unit-acquired urinary tract infections

PURPOSE OF REVIEW: The development of urinary tract infections in critically ill adult patients is associated with considerable morbidity, prolonged hospitalization, and greater healthcare expenditures. We review the occurrence, microbiology, risk factors for acquisition, and outcomes associated with intensive care unit-acquired urinary tract infections. RECENT FINDINGS: Reports from several countries indicate that nosocomial urinary tract infections frequently complicate the course of patients admitted to intensive care units. Virtually all patients who develop an intensive care unit-acquired urinary tract infection have indwelling urinary catheters; other factors associated with the development of these infections include increased duration of urinary catheterization, female sex, intensive care unit length of stay, and preceding systemic antimicrobial therapy. The most frequent pathogens include Escherichia coli, Pseudomonas aeruginosa, enterococci, and Candida albicans; both the species distribution and rates of resistance vary considerably among institutions and regions. Secondary bloodstream infections are uncommon. Although acquisition of an intensive care unit-acquired urinary tract infection has been associated with a prolongation of intensive care unit length of stay, higher cost, and a higher crude case fatality rate, they do not appear to independently increase the risk for death. SUMMARY: Urinary tract infection is a common complication of critical illness that is associated with increased patient morbidity but not mortality. There is a relative paucity of research on nosocomial urinary tract infection specifically acquired in the intensive care unit and further studies are needed to better define the epidemiology and management of these infections.     

Global changes in the epidemiology of community-acquired pneumonia

Lower respiratory tract infections are the most common infectious cause of death in the world and the third most common cause of death globally (all causes). This article reviews the epidemiology of community-acquired pneumonia from a global perspective. Major areas of epidemiological work include (1) disease surveillance to define the burden of disease and to document outbreaks, (2) identification of risk factors for a disease to optimize prevention strategies, and (3) comparisons of treatment effects to improve clinical outcomes for patients with the disease.